A phosphorylation-induced turn defines the Alzheimer's disease AT8 antibody epitope on the tau protein

Post mortem biochemical staging of Alzheimer’s disease is currently based on immunochemical analysis of brain slices with the AT8 antibody. The epitope of AT8 is described around the pSer202/pThr205 region of the hyperphosphorylated form of the neuronal protein tau. In this study, NMR spectroscopy w...

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Main Authors: Gandhi, Neha, Landrieu, I., Byrne, C., Kukic, P., Amniai, L., Cantrelle, F., Wieruszeski, J., Mancera, Ricardo, Jacquot, Y., Lippens, G.
Format: Journal Article
Published: Wiley-VCH Verlag 2015
Online Access:http://hdl.handle.net/20.500.11937/8408
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author Gandhi, Neha
Landrieu, I.
Byrne, C.
Kukic, P.
Amniai, L.
Cantrelle, F.
Wieruszeski, J.
Mancera, Ricardo
Jacquot, Y.
Lippens, G.
author_facet Gandhi, Neha
Landrieu, I.
Byrne, C.
Kukic, P.
Amniai, L.
Cantrelle, F.
Wieruszeski, J.
Mancera, Ricardo
Jacquot, Y.
Lippens, G.
author_sort Gandhi, Neha
building Curtin Institutional Repository
collection Online Access
description Post mortem biochemical staging of Alzheimer’s disease is currently based on immunochemical analysis of brain slices with the AT8 antibody. The epitope of AT8 is described around the pSer202/pThr205 region of the hyperphosphorylated form of the neuronal protein tau. In this study, NMR spectroscopy was used to precisely map the AT8 epitope on phosphorylated tau, and derive its defining structural features by a combination of NMR analyses and molecular dynamics. A particular turn conformation is stabilized by a hydrogen bond of the phosphorylated Thr205 residue to the amide proton of Gly207, and is further stabilized by the two Arg residues opposing the pSer202/pThr205.
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institution Curtin University Malaysia
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last_indexed 2025-11-14T06:20:44Z
publishDate 2015
publisher Wiley-VCH Verlag
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spelling curtin-20.500.11937-84082017-09-13T14:35:42Z A phosphorylation-induced turn defines the Alzheimer's disease AT8 antibody epitope on the tau protein Gandhi, Neha Landrieu, I. Byrne, C. Kukic, P. Amniai, L. Cantrelle, F. Wieruszeski, J. Mancera, Ricardo Jacquot, Y. Lippens, G. Post mortem biochemical staging of Alzheimer’s disease is currently based on immunochemical analysis of brain slices with the AT8 antibody. The epitope of AT8 is described around the pSer202/pThr205 region of the hyperphosphorylated form of the neuronal protein tau. In this study, NMR spectroscopy was used to precisely map the AT8 epitope on phosphorylated tau, and derive its defining structural features by a combination of NMR analyses and molecular dynamics. A particular turn conformation is stabilized by a hydrogen bond of the phosphorylated Thr205 residue to the amide proton of Gly207, and is further stabilized by the two Arg residues opposing the pSer202/pThr205. 2015 Journal Article http://hdl.handle.net/20.500.11937/8408 10.1002/anie.201501898 Wiley-VCH Verlag restricted
spellingShingle Gandhi, Neha
Landrieu, I.
Byrne, C.
Kukic, P.
Amniai, L.
Cantrelle, F.
Wieruszeski, J.
Mancera, Ricardo
Jacquot, Y.
Lippens, G.
A phosphorylation-induced turn defines the Alzheimer's disease AT8 antibody epitope on the tau protein
title A phosphorylation-induced turn defines the Alzheimer's disease AT8 antibody epitope on the tau protein
title_full A phosphorylation-induced turn defines the Alzheimer's disease AT8 antibody epitope on the tau protein
title_fullStr A phosphorylation-induced turn defines the Alzheimer's disease AT8 antibody epitope on the tau protein
title_full_unstemmed A phosphorylation-induced turn defines the Alzheimer's disease AT8 antibody epitope on the tau protein
title_short A phosphorylation-induced turn defines the Alzheimer's disease AT8 antibody epitope on the tau protein
title_sort phosphorylation-induced turn defines the alzheimer's disease at8 antibody epitope on the tau protein
url http://hdl.handle.net/20.500.11937/8408